Can diabetic ketoacidosis occur in an adult with type 2 diabetes mellitus, particularly when using SGL‑2 inhibitors or experiencing severe stressors?

Diabetic Ketoacidosis in Type 2 Diabetes

Yes, diabetic ketoacidosis (DKA) absolutely occurs in type 2 diabetes, though less commonly than in type 1 diabetes, and typically requires specific precipitating factors such as severe physiologic stress, SGLT2 inhibitor use, insulin deficiency states, or acute illness. 1

Epidemiology and Clinical Reality

• DKA occurs in type 2 diabetes at a rate of up to 3.2 per 1,000 person-years, which is substantially lower than the 44.5-82.6 per 1,000 person-years seen in type 1 diabetes, but is far from rare. 1

• Type 2 diabetes accounts for 90-95% of all diabetes cases, and while DKA seldom occurs spontaneously in this population, it is a well-recognized complication that should never be dismissed based on diabetes type alone. 1

• Approximately 10% of all DKA cases present with euglycemic DKA (plasma glucose <200 mg/dL), making diagnosis particularly challenging in type 2 diabetes patients, especially those on SGLT2 inhibitors. 1

Major Precipitating Factors

Severe Physiologic Stress

• Acute infections (particularly urinary tract infections and pneumonia), myocardial infarction, trauma, and surgery are the most common triggers, with infection accounting for 30-50% of DKA cases across all diabetes types. 2

• COVID-19 and other severe intercurrent illnesses can precipitate DKA in type 2 diabetes patients who would otherwise maintain adequate glycemic control. 1

SGLT2 Inhibitor-Associated DKA

• SGLT2 inhibitors increase DKA risk with a relative risk of 2.46 (95% CI 1.16-5.21) in randomized controlled trials and 1.74 (95% CI 1.07-2.83) in observational studies, though the absolute incidence remains low at 0.6-4.9 events per 1,000 patient-years. 1, 3

• Risk factors for SGLT2 inhibitor-associated DKA include: very-low-carbohydrate diets, prolonged fasting, dehydration, excessive alcohol intake, insulin dose reduction >20%, acute illness, and presence of autoimmunity (latent autoimmune diabetes in adults misdiagnosed as type 2 diabetes). 3, 4

• SGLT2 inhibitors should be discontinued at least 3 days before elective surgery or procedures requiring fasting to prevent perioperative euglycemic DKA. 3

Insulin Deficiency States

• Patients with type 2 diabetes already on insulin therapy who miss or take inadequate doses are at significant risk for DKA, particularly when combined with other stressors. 1, 5

• Ketosis-prone type 2 diabetes, a specific subtype more common in ethnic minorities (particularly African Americans and Hispanics), carries inherently higher DKA risk even without obvious precipitants. 5

Other Medication-Related Triggers

• Glucocorticoids and second-generation antipsychotics can precipitate DKA by increasing insulin resistance and counter-regulatory hormones. 1, 3

• Illicit drug use, particularly cocaine, has been associated with DKA in type 2 diabetes. 1

Critical Diagnostic Considerations

• Do not assume DKA cannot occur based on a type 2 diabetes diagnosis alone—this is a dangerous clinical pitfall, particularly in ethnic minorities who may present with DKA despite having type 2 diabetes. 5

• All diagnostic criteria for DKA must be met: either hyperglycemia (glucose ≥200 mg/dL) OR prior diabetes history, PLUS metabolic acidosis (pH <7.3, bicarbonate <15 mEq/L), PLUS ketonemia or ketonuria. 1

• Euglycemic DKA requires high clinical suspicion in patients on SGLT2 inhibitors presenting with nausea, vomiting, abdominal pain, or generalized weakness, even with glucose <200 mg/dL. 1, 6

• Approximately 10% of patients present with mixed DKA-HHS features, combining ketoacidosis with severe hyperglycemia, hyperosmolality, and dehydration. 1

Clinical Severity and Outcomes

• DKA in type 2 diabetes is associated with worse outcomes compared to type 1 diabetes, with higher rates of severe DKA (25.7% vs 9.0%) and increased mortality. 7

• Advanced age, mechanical ventilation, and bed-ridden state are independent predictors of 30-day mortality in type 2 diabetes patients with DKA. 7

• Type 2 diabetes patients with DKA require longer treatment times (36.0 vs 28.9 hours) to achieve ketone-free urine compared to type 1 diabetes patients. 5

Prevention Strategies

For All Type 2 Diabetes Patients

• Patients on intensive insulin therapy must never stop or hold basal insulin, even when not eating, as this is a critical precipitant of DKA. 1

• Provide detailed sick day management instructions including when to temporarily discontinue SGLT2 inhibitors during acute illness, dehydration, or prolonged fasting. 3

For SGLT2 Inhibitor Users

• Avoid substantial insulin dose reductions (>20%) when initiating SGLT2 inhibitors, as this can tip patients into an insulinopenic state. 3

• Educate patients to seek immediate medical attention for symptoms of DKA (nausea, vomiting, abdominal pain, weakness) and to check ketones during high-risk situations. 3

• Temporarily discontinue SGLT2 inhibitors during acute illness, surgery, or prolonged fasting, and ensure patients understand these sick day rules. 3, 4

Key Clinical Pitfall

The most dangerous assumption is that euglycemic or mildly elevated glucose levels exclude DKA in type 2 diabetes patients on SGLT2 inhibitors—this leads to delayed diagnosis and treatment of a life-threatening condition. 6, 8 Always check ketones and venous blood gas in symptomatic patients regardless of glucose level.